At the request of NIMH (Division of Neuroscience and Basic Behavioral Science, Dr. Douglas Meinecke), this Supplemental application corresponds to Funded Years 03 and 04 of "Hippocampal Atrophy in Major Depression (RO1 MH 67996; PI: C. Stockmeier). The request for Supplemental support to continue and expand tissue collection is an extension of Supplemental Postmortem Brain Collection funding (NOT-MH-01- 010) awarded to Dr. Gregory Ordway as part of RO1 63187 (06/01/02 -11/30/05), and 11 years of NIMH funding for collection to the PI prior to that. Neuroimaging and postmortem brain studies provide evidence for hippocampal pathology in major depressive disorder (MDD). It is hypothesized that a decrease in hippocampal neuropil, in response to diminished markers of neural growth and synaptic connection, resulting in an increase in neuronal and glial density, is the microscopic basis for the histopathology of the hippocampus in MDD. To meet the Specific Aims of the parent RO1 (MH 67996), supplemental funds are requested for the collection of 1) human brain tissue at autopsy and 2) sufficient clinical information from next-of-kin and medical records for retrospective assessment of DSM-IV psychiatric disorders. With informed written consent, brain tissue is sought from subjects suffering a major depressive episode in the last two weeks of life and psychiatrically-normal control subjects matched for age, gender, postmortem interval arid tissue pH. These depressed subjects will not be receiving antidepressant or antipsychotic treatment at the time of death and all subjects must be neurologically and neuropathologically normal. Subjects with MDD must have no current co-morbid Axis I diagnosis of an alcohol or psychoactive substance use disorder. The presence or absence of MDD is determined by consensus diagnosis based on medical records and data gathered from next-of-kin of all subjects with the Structured Clinical Interview for DSM IV Psychiatric Disorders (SCID). At current collection rates, the collection of 6-8 subjects with MDD and about 10 normal control subjects per year for the next two years will permit achievement of the funded specific aims. Current NIH funding to Drs.C. Stockmeier, G. Ordway, G. Rajkowska, R. Duman, B. Karolewicz and M. Austin depends solely on this Supplement for brain tissue to better understanding of the cellular and molecular pathophysiology of the major mental illnesses. [unreadable] [unreadable]